| Environmental cold exposure has significant effect on the strength of the army. Many well-known winter wars in the history have demonstrated that cold may be key factor in the development of the war. With large cold areas in China, and half of the population and about 2/3 troops in these areas, it's very important to investigate the measures to enhancing the adaptation to cold and capability of military operations.Cold is a common environmental risk that is likely to occur in civilian occupational or leisure-time activities. People are inevitably in contact with natural or artificial low temperature in daily life or at work. Cold can induce stress responses and bring a series of specific or nonspecific biological effects. Long time exposure to cold environment may lead to impairment in cardiovascular system, immune system, central nerve system and articuli. Liver is the main organ for energy metabolism. Exposure to cold environment may result in increased level of lipid peroxidation, changed enzymatic activity, glycogenolysis, and decreased activity of immunocytes in the liver, indicating that the function of the liver may changed in the cold environment. However, its molecular mechanism is unclear. The regulation of liver function plays a crucial in the adaptation to cold. The cyclin-dependent kinase inhibitor p21,is critical for regulation of the cell cyele and DNA replication. It plays a role in cell differentiation,seneseenee and aptosis. In the present study, through in vivo and in vitro experiments, we investigated the impairments of liver exposed to cold and its molecular mechanisms. The findings of the current study will improve the knowledge of the mechanisms of liver impairments induced by cold exposure and provide bases for the protection.[Method]1.Rats were put at -15℃for 6 h per day. The histopathological changes of the rat liver were observed by hematoxylin and eosin staining; Western blot was performed to determine the expression and phosphorylation of MAPKs signaling molecules.2.Chang liver cell were cultured at 4℃for 0 h to 24 h. The morphological changes of the cells were observed using the inverted microscope. The cell viability was determined by MTT assay and Trypan blue exclusion test. Flow cytometry and TUNEL staining were performed to detect apoptotic cells. Western blot was performed to determine the expression of cyclins, MAPKs, and mTOR under the cold exposure. SP600125 and rapamycin were used to block the JNK pathway and mTOR pathway, respectively, and then the change of cell cycle and the expression of cyclins were observed.[Result]1.HE staining showed that morphological changes were significant after the cold exposure in the time-dependent manner. Western blot demonstrated that the cold exposure significantly increased the level of phosphorylated JNK; however, the level of phosphorylated ERK remained unchanged.2.Live cell counting, MTT assay and Trypan blue exclusion test showed that after the cold exposure, the cell proliferation was significantly arrested time-dependently. Flow cytometry and TUNEL showed that there were more apoptotic cells after the cold exposure. Western blot also showed that the level of caspase-3 remained unchanged. Flow cytometry showed the significantly suppressed cell cycle in S phase. Western blot showed the significantly down-regulated expression of p21. The phosphorylation of JNK and mTOR Ser2446 were significantly up-regulated. In addition, the mTOR inhibitor partly reversed the S phase suppression and the decrease of p21 level; however, SP600125, a specific JNK inhibitor, didn't show any influence on cell cycle.[Conclusion]1.Cold stress can induce rat liver damage. Long time exposure to cold may result in impairments of liver structure and functions in a time-dependent manner. The cold also leads to increased level of phosphorylated JNK; however, the expression and phosphorylation of ERKremained remain unchanged, indicating that JNK may be involved in the cold exposure-induced liver impairment.2.Exposure of Chang liver cells at 4℃can result in proliferation arrest, but don't induce cell apoptosis. Cold exposure can lead to S phase suppression, accompanied by decreased p21 level. mTOR signaling pathway may be involved in the regulation of cell cycle under cold exposure. The increase of JNK phosphorylation may just be a response under the cold stress.
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